Photodiagnosis and Photodynamic Therapy (2015) 12, 176—185 Available online at www.sciencedirect.com ScienceDirect jo ur nal ho mepage: www.elsevier.com/locate/pdpdt Photodynamic efficiency of hypericin compared with chlorin and hematoporphyrin derivatives in HEp-2 and Vero epithelial cell lines Claudia Bernal a , Anderson O. Ribeiro b , Gislaine P. Andrade b , Janice R. Perussi a,* a Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil b Centro Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil Received 4 August 2014; received in revised form 8 April 2015; accepted 10 April 2015 Available online 22 April 2015 KEYWORDS Photodynamic therapy; Cancer cells; Hypericin; Hematoporphyrin derivative; Chlorin derivative Summary Hypericin (HY) is a photoactive aromatic dianthraquinone that is considered a potent photodynamic agent. In this study, hypericin and two other photosensitizers, a hemato- porphyrin derivative (Photogem ® ; PG) and a chlorin derivative (Photodithazine ® ; PZ), were compared in terms of their phototoxicity toward two cell lines, HEp-2 and Vero. The median inhibitory concentration (IC 50 ) of each of the photosensitizers was obtained after a 16.2 J cm -2 dose of irradiation at 630 ± 10 nm. The IC 50 values were 0.07 ± 0.01 (HY), 1.0 ± 0.2 (PZ), and 9 ± 1 g mL -1 (PG) in HEp-2 cells and 0.3 ± 0.1 (HY), 1.6 ± 0.2 (PZ) and 11 ± 1 g mL -1 (PG) in Vero cells, showing that HY is more phototoxic than the others when irradiated at 630 nm. If these results are analyzed, simultaneously, with the first-order constant for BSA tryptophan pho- tooxidation, obtained by fluorescence decay ( excitation = 280 nm), which are 11 × 10 -3 min -1 ± 1. 10 -3 min -1 (HY), 10 × 10 -3 min -1 ± 1 × 10 -3 min -1 (PZ), and 6 × 10 -3 min -1 ± 1 × 10 -3 min -1 (PG), it is possible to infer that the photodynamic efficiency alone is not sufficient to explain the higher HY phototoxicity. The lipophilicity is also an important factor for an efficient target cell accumulation and was assessed for all sensitizers through the octanol—water partition coeffi- cient (log P): 1.20 ± 0.02 (HY), -0.62 ± 0.03 (PZ), and -0.9 ± 0.2 (PG). The higher value for HY correlates well with its observed superior efficiency to promote damage at low concentrations and doses. As HY is used for the long-term treatment of mild depression, it is considered safe for Abbreviations: PDT, photodynamic therapy; ROS, reactive oxygen species; SDS, sodium dodecyl sulfate; UA, uric acid; PBS, phosphate buffered saline; DMSO, dimethyl sulfoxide; HY, hypericin; PG, Photogem; PZ, Photogem. ∗ Corresponding author. Tel.: +55 1633739956; fax: +55 1633739985. E-mail address: janice@iqsc.usp.br (J.R. Perussi). http://dx.doi.org/10.1016/j.pdpdt.2015.04.003 1572-1000/© 2015 Elsevier B.V. All rights reserved.